The major objective of the proposed research is to evaluate the carcinogenic potential and mechanism of action of congeners of polychlorinated biphenyls (PCBs). The rates and routes of excretion and identification of hydroxylation, dechlorination, and arene oxide formation will be evaluated utilizing thin layer, high pressure liquid, and gas liquid chromatography and mass, nuclear magnetic resonance, and infrared spectroscopy. An in vitro system utilizing microsomes will be used to generate PCB metabolites. Chemical synthesis of metabolites with probable carcinogenic activity, arene oxides, will be done. Tumor induction will be evaluated by long term exposure of rats, with or without partial hepatectomy, to diets containing mixtures or single PCBs; application of PCBs or metabolites to skin of mice followed by promotion; injection of PCBs or metabolites into the portal or systemic venous system. The binding capacity of PCB metabolites with cellular constituents will be evaluated and the mechanism of interaction will be examined by the isolation and analysis of the complex. The ability of PCBs to cause malignant transformation of cell cultures will be evaluated by exposing cultures of an embryonic fibroblast cell line or of a primary liver cell line to PCBs or metabolites. Transformed cells will be injected into a susceptible host for the evaluation of tumor formation.